John Mizerock's journey in professional baseball began when he was drafted by the Houston Astros in the first round of the 1979 Major League Baseball Draft. As a catcher, Mizerock's career in the major leagues spanned several seasons, during which he played for both the Houston Astros and the Atlanta Braves.

Mizerock made his major league debut with the Astros in 1983. Over the next few years, he played intermittently for Houston, primarily serving as a backup catcher. His time with the Astros was marked by limited playing opportunities, as he was often behind established catchers on the roster. Despite this, Mizerock's presence on the team provided depth to the catching position.

In 1986, Mizerock was traded to the Atlanta Braves, where he continued his role as a backup catcher. His tenure with the Braves lasted until 1989, during which he appeared in a modest number of games each season. While his batting statistics were not remarkable, Mizerock's defensive skills and ability to work with pitchers were valued by his teams.

After his playing days in the major leagues concluded, Mizerock transitioned into coaching and managing within the minor league system. He began his coaching career in the Kansas City Royals organization, where he managed various minor league teams. His managerial roles included stints with the Wilmington Blue Rocks, Wichita Wranglers, and Omaha Royals. Mizerock's experience as a former major league player provided him with insights that he could pass on to younger players.

In 2002, Mizerock briefly served as the interim manager for the Kansas City Royals at the major league level. Although his time as manager was short-lived, it demonstrated the trust the organization had in his leadership abilities. Following this, he continued to work within the Royals' system in various coaching capacities.